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Fidaxomicin for clostridium difficile-associated diarrhoea: epidemiological method for estimation of warranted price |
Sclar DA, Robison LM, Oganov AM, Schmidt JM, Bowen KA, Castillo LV |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. CRD summary The objective was to determine whether fidaxomicin was good value for money in the treatment of Clostridium difficile-associated diarrhoea. The authors concluded that, from the perspective of the US health system, fidaxomicin was good value for money. The methods were novel and the assessment of the effectiveness of the treatments was limited, making validity judgements difficult. The authors' conclusion appears to reflect the scope of the analysis, but should not be considered to be robust. Type of economic evaluation Cost-effectiveness analysis Study objective The objective was to determine whether fidaxomicin was good value for money in the treatment of Clostridium difficile-associated diarrhoea. Interventions Fidaxomicin 200mg, twice daily, was compared with three vancomycin regimens. The regimens were 125mg injectable vancomycin, orally four times daily, with vancomycin hydrochloride capsules 125mg, four times daily, after hospital discharge; vancomycin hydrochloride 125mg capsules, four times daily; or 250mg capsules, four times daily. Treatment began on the first day of hospital admission and continued for 10 days. Location/setting USA/primary and secondary care. Methods Analytical approach:The clinical data from two randomised controlled trials (RCTs) were combined with economic data, to assess the net savings or costs of the treatments, over 25 days. The authors stated that a US health system perspective was adopted. Effectiveness data:The key effectiveness estimate was the number-needed-to-treat with fidaxomicin, for a sustained clinical response, compared with vancomycin hydrochloride. A sustained clinical response was defined as a clinical response after treatment, with survival without proven or suspected Clostridium difficile-associated diarrhoea recurrence up to 25 days after the end of treatment. The efficacy data were from two RCTs, with 596 patients and 509 patients. These RCTs included 10 days of treatment with either fidaxomicin 200mg twice daily or vancomycin hydrochloride 125mg four times daily. The results of the RCTs were pooled to derive a single number-needed-to-treat estimate. Monetary benefit and utility valuations:Not relevant. Measure of benefit:The benefit was measured by the comparative number-needed-to-treat. Cost data:The mean hospital stay and mean cost, for the mix of primary and secondary cases of Clostridium difficile-associated diarrhoea, were from the 2009 US Healthcare Cost and Utilization Project. For secondary cases, 18% of hospital stay and 46% of hospital costs were attributed directly to the diarrhoea, based on a published study. The costs were reported in 2011 US $. Net savings or losses to the health system per day were calculated by sequentially combining information on the number-needed-to-treat, the market price of fidaxomicin, the hospital cost of primary or secondary cases, the hospital stay, and the cost of vancomycin for primary or secondary cases. This was then used to determine the warranted (justifiable) price per day for fidaxomicin, as a percentage of its wholesale acquisition cost per day ($280). Analysis of uncertainty:Variability in the hospital stay was presented using standard errors. Results The pooled number-needed-to-treat for a sustained clinical response was 7.1. For primary cases, fidaxomicin resulted in a loss of $916.57 per day, compared with injectable vancomycin, a loss of $216.57 per day, compared with 125mg vancomycin capsules, and a gain of $683.43 per day, compared with 250mg vancomycin capsules. For secondary cases, fidaxomicin resulted in a gain of $211.29 per day compared with injectable vancomycin, $511.29 per day compared with 125mg capsules, and $1,411.29 per day compared with 250mg capsules. For the mixture of cases, the warranted price per day for fidaxomicin was 95% of its wholesale acquisition cost per day, compared with injectable vancomycin; 109% compared with 125mg vancomycin capsules; and 141% compared with 250mg capsules. Authors' conclusions The authors concluded that, from the perspective of the US health system, fidaxomicin was good value for money. CRD commentary Interventions:The intervention and comparator were clearly stated. The authors justified their choice for these, stating that fidaxomicin had been recently approved, by the US Food and Drug Administration, for the treatment of Clostridium difficile-associated diarrhoea, and vancomycin was recommended in 2010 guidelines. The authors mentioned that metronidazole was recommended in these guidelines; they did not justify its exclusion from the analysis. It was not clear if vancomycin was the usual care, and if all relevant comparators were considered. Effectiveness/benefits:Limited details of the trials used to derive the efficacy estimate were reported. The trials were reported to have good methods, so bias should be minimised. The methods used to identify and select them were not reported, making it unclear if other evidence was available. The main efficacy estimate was clearly reported. The trials assessed one regimen of vancomycin, and it is unclear if it was appropriate to apply this pooled efficacy to the alternative regimens considered in the analysis. A limitation of the analysis was the measure of benefit. The number-needed-to-treat only provided information on readmission rates over a short period, limiting its assessment of the benefits and harms of each treatment. There was no information on adverse events and the quality of life of the patients. The aim of the analysis was to estimate the warranted price and this was the focus of the reporting. Costs:The cost results were clearly reported, but the individual cost items were not. National data were used for primary and secondary cases, and a published method was used to attribute the part of the hospital stay due to secondary cases. These sources are likely to have been appropriate for the authors' setting and perspective adopted. The drug costs were in 2011 US $, but the source for each individual cost was unclear. Analysis and results:The calculations of the net savings or costs, and associated warranted prices, were clearly reported. The analysis had a short time horizon of 25 days; if the costs and effects of the treatments were expected to extend beyond this, then the time horizon was inappropriate. No analysis of the effects of parameter uncertainty on the results was conducted. So no conclusions on the certainty of the results can be made. The authors stated that prospective research was required to confirm their findings. Concluding remarks:The study methods were novel, and the aim of the analysis should be considered when assessing the conclusions. The assessment of the effectiveness of the treatments was limited, as the focus was to discern the fiscal utility of fidaxomicin. The authors' conclusion reflects the scope of the analysis undertaken, but should not be considered to be robust. Funding Supported by Optimer Pharmaceuticals, Inc., manufacturer of fidaxomicin. Bibliographic details Sclar DA, Robison LM, Oganov AM, Schmidt JM, Bowen KA, Castillo LV. Fidaxomicin for clostridium difficile-associated diarrhoea: epidemiological method for estimation of warranted price. Clinical Drug Investigation 2012; 32(8): e17-e24 Indexing Status Subject indexing assigned by NLM MeSH Aminoglycosides /therapeutic use; Clostridium Infections /drug therapy /epidemiology /microbiology; Clostridium difficile /isolation & Humans; Length of Stay; United States /epidemiology; purification AccessionNumber 22012028162 Date bibliographic record published 19/04/2013 Date abstract record published 21/06/2013 |
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